Single-cell RNA sequencing identifies molecular targets associated with poor in vitro maturation performance of oocytes collected from ovarian stimulation.

STUDY QUESTION: What is the transcriptome signature associated with poor performance of rescue IVM (rIVM) oocytes and how can we rejuvenate them? SUMMARY ANSWER: The GATA-1/CREB1/WNT signalling axis was repressed in rIVM oocytes, particularly those of poor quality; restoration of this axis may produce more usable rIVM oocytes. WHAT IS KNOWN ALREADY: rIVM aims to produce mature oocytes (MII) for IVF through IVM of immature oocytes collected from stimulated ovaries. It is not popular due to limited success rate in infertility treatment. Genetic aberrations, cellular stress and the absence of cumulus cell support in oocytes could account for the failure of rIVM. STUDY DESIGN, SIZE, DURATION: We applied single-cell RNA sequencing (scRNA-seq) to capture the transcriptomes of human in vivo oocytes (IVO) (n = 10) from 7 donors and rIVM oocytes (n = 10) from 10 donors. The effects of maternal age and ovarian responses on rIVM oocyte transcriptomes were also studied. In parallel, we studied the effect of gallic acid on the maturation rate of mouse oocytes cultured in IVM medium with (n = 84) and without (n = 85) gallic acid. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human oocytes were collected from donors aged 28-41 years with a body mass index of <30. RNA extraction, cDNA generation, library construction and sequencing were performed in one preparation. scRNA-seq data were then processed and analysed. Selected genes in the rIVM versus IVO comparison were validated by quantitative real-time PCR. For the gallic acid study, we collected immature oocytes from 5-month-old mice and studied the effect of 10-µM gallic acid on their maturation rate. MAIN RESULTS AND THE ROLE OF CHANCE: The transcriptome profiles of rIVM/IVO oocytes showed distinctive differences. A total of 1559 differentially expressed genes (DEGs, genes with at least 2-fold change and adjusted P < 0.05) were found to be enriched in metabolic processes, biosynthesis and oxidative phosphorylation. Among these DEGs, we identified a repression of WNT/ß-catenin signalling in rIVM when compared with IVO oocytes. We found that oestradiol levels exhibited a significant age-independent correlation with the IVO mature oocyte ratio (MII ratio) for each donor. rIVM oocytes from women with a high MII ratio were found to have over-represented cellular processes such as anti-apoptosis. To further identify targets that contribute to the poor clinical outcomes of rIVM, we compared oocytes collected from young donors with a high MII ratio with oocytes from donors of advanced maternal age and lower MII ratio, and revealed that CREB1 is an important regulator. Thus, our study identified that GATA-1/CREB1/WNT signalling was repressed in both rIVM oocytes versus IVO oocytes and in rIVM oocytes of lower versus higher quality. Consequently we investigated gallic acid, as a potential antioxidant substrate in human rIVM medium, and found that it increased the mouse oocyte maturation rate by 31.1%. LARGE SCALE DATA: Raw data from this study can be accessed through GSE158539. LIMITATIONS, REASONS FOR CAUTION: In the rIVM oocytes of the high- and low-quality comparison, the number of samples was limited after data filtering with stringent selection criteria. For the oocyte stage identification, we were unable to predict the presence of oocyte spindle, so polar body extrusion was the only indicator. WIDER IMPLICATIONS OF THE FINDINGS: This study showed that GATA-1/CREB1/WNT signalling was repressed in rIVM oocytes compared with IVO oocytes and was further downregulated in low-quality rIVM oocytes, providing us the foundation of subsequent follow-up research on human oocytes and raising safety concerns about the clinical use of rescued oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Collaborative Research Fund, Research Grants Council, C4054-16G, and Research Committee Funding (Research Sustainability of Major RGC Funding Schemes), The Chinese University of Hong Kong. The authors have no conflicts of interest to declare.

Impact of denosumab on cardiovascular calcification in patients with secondary hyperparathyroidism undergoing dialysis: a pilot study.

The receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK/osteoprotegerin system is dysregulated in hyperparathyroid bone diseases. The introduction of denosumab preceding elective surgery as an alternative option when surgery is not possible immediately. INTRODUCTION: The effects of denosumab on vascular calcification in patients with chronic renal failure and low bone mass have been a subject of interest. Therefore, this investigation aimed to determine the short-term changes in vascular calcification after denosumab treatment using a serial electrocardiography-gated computed tomography (CT) to measure coronary artery calcification (CAC) in patients with secondary hyperparathyroidism (SHPT) and low bone mass. METHODS: This 6-month study enrolled patients with SHPT and low bone mass (T-score < - 2.5) owing to dialysis. The 2 groups administered denosumab at a dose of 60 mg (denosumab group), and conventional treatment (control group) had 21 patients each. All patients underwent CT scans at baseline and at the follow-up examination at 6 months to determine the bone mineral density and CAC. RESULTS: The control group demonstrated a significant increase in Agatston scores (187.79 ± 72.27) (P = 0.004). However, no significant change was noted in the denosumab group (P = 0.41). In the denosumab group, only the baseline serum alkaline phosphatase levels correlated negatively with changes in the CAC score (P = 0.01); the baseline alkaline phosphatase levels were the deciding biomarkers for non-responsive CAC scores by Berry Criteria after denosumab treatment (P = 0.02). The denosumab group demonstrated significantly increased bone mineral density in the femoral neck and lumbar spine (P < 0.01). CONCLUSION: The findings provide evidence that denosumab may suppress the progression of CAC and also regress osseous calcification in severe cases of high bone turnover.

Severe hypophosphatemia induced by denosumab in a patient with osteomalacia and tenofovir disoproxil fumarate-related acquired Fanconi syndrome.

Denosumab, a novel agent that inhibits osteoclasts, reduces the risk of fracture in patients with osteoporosis. However, worsening of hypophosphatemia and other symptoms may be induced by denosumab in patients with pre-existing hypophosphatemic osteomalacia. A 58-year-old man with hepatitis B presented with diffuse bone pain and muscle weakness. Denosumab was prescribed by the orthopedist according to documented low bone mass and spine compression fracture. After administering denosumab, the patient's bone pain worsened, and he later developed a right tibia stress fracture. His condition was diagnosed as adult-onset hypophosphatemic osteomalacia complicated by multiple bone fractures, which resulted from Fanconi syndrome with proximal tubulopathy due to tenofovir disoproxil fumarate (TDF) treatment for his hepatitis B. Denosumab use leads to aggressive hypophosphatemic osteomalacia and the complication of stress fractures, because of its effects on bone resorption. Physicians should be aware that in patients with chronic hepatitis B monoinfection who are administered TDF therapy, bone pain or fracture is possible but preventable by timely monitoring of serum phosphate levels. Denosumab should not be used in patients with untreated osteomalacia or vitamin D deficiency, as it may lead not only to hypocalcemia but also to hypophosphatemia in these patients.

Better adherence to antithyroid drug is associated with decreased risk of stroke in hyperthyroidism patients.

BACKGROUND: An increased risk for ischaemic stroke has been reported in young hyperthyroidism patients independent of atrial fibrillation (AF). However, whether the use of antithyroid drugs in hyperthyroidism patients can reduce the occurrence of ischaemic stroke remains unclear. METHODS: A total of 36,510 newly diagnosed hyperthyroidism patients during 2003-2006 were identified from the Taiwan National Health Insurance Research database. Each patient was individually tracked for 5 years from their index date (beginning the antithyroid drugs) to identify those who suffered from new episode of ischaemic stroke. Medication possession ratio (MPR) was used to represent the antithyroid drug compliance. The association between the MPR and the risk of stroke was examined. RESULTS: The stroke incidence rates for hyperthyroidism patients with age < 45 years and age ≥ 45 years were 0.42 and 3.76 per 1000 person-years, respectively. The patients aged < 45 years with MPR < 0.2 (adjusted hazard ratio, HR, 2.30; 95% CI, 1.13-4.70; p = 0.02) and 0.2 ≤ MPR < 0.4 (adjusted HR, 2.24; 95% CI, 1.06-4.72; p = 0.035) had a significantly increased risk of ischaemic stroke as compared to those with ≥ 0.6. In patients of the age ≥ 45 years, only the patients with MPR < 0.2 (adjusted HR, 1.44; 95% CI, 1.03-2.01; p = 0.036) had a significantly higher risk of ischaemic stroke as compared to those with MPR ≥ 0.6. In hyperthyroidism patients without AF, good antithyroid drugs compliance also reduced the incidence of stroke significantly (adjusted HR, range: 1.52-1.61; p = 0.02); but not in hyperthyroidism with AF. CONCLUSION: Hyperthyroidism patients with good antithyroid drug compliance had a lower risk of ischaemic stroke than patients with poor compliance.

Impact of homocysteine on cortical perfusion and cognitive decline in mild Alzheimer's dementia.

BACKGROUND AND PURPOSE: Elevated plasma total homocysteine level (tHcy) is associated with increased risk of dementia via increased white matter changes or reduction in cortical volume. Whether tHcy has an independent impact on regional perfusion and if it can predict a more rapid cognitive decline in mild Alzheimer dementia (AD) warrants investigation. METHODS: Eighty AD patients with a clinical dementia rating of 1 were enrolled. Their Cognitive Ability Screening Instrument (CASI) scores on enrolment and after 1 year of follow-up as well as their perfusion index (PI) from single photon emission computed tomography upon enrolment were analyzed. RESULTS: In cross-sectional analysis, elevated tHcy was associated with lower frontal PI independent of cerebrovascular risk factors (ß = -0.35, P = 0.009). The CASI scores correlated with temporo-parietal PI (Pearson r range 0.3-0.39, P < 0.01) but not with tHcy or frontal PI. By longitudinal analysis, only tHcy level was related to a more rapid cognitive decline (odds ratio for executive function score 1.82; odds ratio for total CASI score 1.74). CONCLUSIONS: Cognitive performance in mild AD can be reflected by hypo-perfusion of the temporo-parietal region while frontal hypo-perfusion may be mediated by tHcy. tHcy level is an independent risk factor for rapid cognitive decline, especially in the executive function.

Inflammasomes are differentially expressed in cardiovascular and other tissues.

To determine the expression of components in Toll-like receptors (TLRs)/Nod-like receptors (NLRs)/inflammasome/caspase-1/interleukin (IL-1)-beta pathway, we examined the expression profiles of those genes by analyzing the data from expression sequence tag cDNA cloning and sequencing. We made several important findings: firstly, among 11 tissues examined, vascular tissues and heart express fewer types of TLRs and NLRs than immune and defense tissues including blood, lymph nodes, thymus and trachea; secondly, brain, lymph nodes and thymus do not express proinflammatory cytokines IL-1beta and IL-18 constitutively, suggesting that these two cytokines need to be upregulated in the tissues; and thirdly, based on the expression data of three characterized inflammasomes (NALP1, NALP3 and IPAF inflammasome), the examined tissues can be classified into three tiers: the first tier tissues including brain, placenta, blood and thymus express inflammasome(s) in constitutive status; the second tier tissues have inflammasome(s) in nearly-ready expression status (with the requirement of upregulation of one component); the third tier tissues, like heart and bone marrow, require upregulation of at least two components in order to assemble functional inflammasomes. Our original model of three-tier expression of inflammasomes would suggest a new concept of tissue inflammation privilege, and provides an insight to the differences among tissues in initiating acute inflammation in response to stimuli.

Distinguishing between two sympatric Acanthopagrus species from Dapeng Bay, Taiwan, using morphometric and genetic characters.

Morphometric and genetic data were used to compare two sympatric and morphologically similar species, Acanthopagrus berda and Acanthopagrus taiwanensis, in Dapeng Bay, South-western Taiwan. A principle component analysis of morphological data indicated a distinction between the two species, with pectoral fin length and eye diameter accounting for 32.27% of the variation. Interspecific sequence divergence, based on mtDNA cytochrome b (0.118 +/- 0.01), was larger than intraspecific divergences between haplotypes (0.007 for A. taiwanensis and 0.003 for A. berda). Individuals of the two species clustered into different groups in three phylogenetic trees with 100% bootstrap support. The mean observed heterozygosity for eight microsatellite loci was 0.471 +/- 0.202 for A. taiwanensis and 0.637 +/- 0.145 for A. berda. Nei's unbiased measure of interspecific genetic distance (D(S)) was 1.334. F(ST) (0.134) and R(ST) (0.404) values indicated significant differentiation between species. An unrooted neighbour-joining tree was constructed by allele-sharing distances and the factorial correspondence analysis split all specimens into two distinct clusters. The results of morphometric, mtDNA and microsatellite analyses indicated the presence of two species, A. taiwanensis and A. berda.

Redshift of edge emission from AlGaInP light-emitting diodes and correlation with electron-hole recombination lifetime.

The edge emission from AlGaInP light-emitting diodes showed a red-shifted peak in addition to the peak of surface emission. This shift resulted from the quantum-well absorption of the guided wave. Although the shift degrades the color quality and the extraction efficiency of the device, it helps elucidate many important optical properties of the material and the dynamics of carrier recombination, including the electron-hole recombination lifetime, the optical joint density of state, the spontaneous emission spectrum and the absorption spectrum. A simple concept of the bimolecular recombination is established. The corresponding coefficient can be expressed by a simple formula and was therefore determined.

Transition of absolute instability from global to local modes in a gyrotron traveling-wave amplifier.

The gyrotron traveling-wave amplifier employing the distributed-loss scheme is capable of very high gain and effective in suppressing the global absolute instabilities. This study systematically characterizes the local absolute instabilities and their transitional behavior. The local absolute instabilities are analyzed using a model that incorporates the penetration of the field from the copper section into the lossy section. The axial modes were characterized from the perspective of beam-wave interaction and were found to share many characteristics with the global modes. The transition from global modes to local modes as the distributed loss increases was demonstrated. The electron transit angle in the copper section, which determines the feedback criterion, governs the survivability of an oscillation. In addition, the oscillation thresholds predicted using this model are more accurate than those obtained using a simplified model.

Multiple isoforms of metallothionein are expressed in the porcine liver.

Isogenes are highly homologous to each other and are often difficult to ascertain, as has been the case with metallothionein, a metal-binding protein rich in cysteines. Conventional separation of metallothionein isoforms relied on ion exchange chromatography of the proteins, or screening for the sequences from gene libraries. In this study, a combination of RT-PCR and partial protein sequencing is used in the identification of metallothionein isogenes expressed in porcine liver. By this approach, we have identified expressed coding sequences which constitute 10 new isogenes. Of the four known groups of metallothioneins (MT), phylogenetic analyses place these pig isogenes in the MT-1 group, except two which are identified as being closely related to MT-2, and none in groups 3 and 4. The isogenes are thus namedpMT-1a to -1g, andpMT-2a and -2b. While each of the isogene sequences is unique, two isogenes,pMT-1e1 andpMT-1e2, share an identical amino acid sequence, differing only in specific codons. Two others,pMT-1b andpMT-1g, have a cysteine substituted by arginine, the first such sequence ever detected in MT.pMT-2a andpMT-2b are closely aligned with the MT-2 group of vertebrates, in spite of the absence of a characteristic acidic amino acid at position 10 or 11, common in other mammalian metallothioneins.

Multiplanar reconstruction in magnetic resonance evaluation of the knee. Comparison with film magnetic resonance interpretation.

RATIONALE AND OBJECTIVES: At many institutions, three-dimensional magnetic resonance imaging (MRI) is routinely used for examination of the knee. Multiplanar reconstruction (MPR) is a method of displaying three-dimensional datasets. The authors assessed the usefulness of MPR for evaluating knee MRI datasets by comparing readers' performance using MPR and conventional film MRIs. METHODS: Eight patients with internal derangement of the knee were studied. All had MRI datasets acquired in the sagittal plane using a three-dimensional gradient-echo fast imaging with steady-state precession (FISP) sequence. Arthroscopic surgery after MRI confirmed the presence of 6 anterior cruciate ligament (ACL) tears, 11 meniscal tears, and 5 normal menisci in this group. Four blinded readers, experienced in MRI of the knee, evaluated the images. The MRI datasets were then loaded onto a three-dimensional workstation and interpreted by the same readers using MPR. The MRI findings were correlated with arthroscopy. RESULTS: For diagnosis of tears of the ACL, sensitivity was 96% and specificity was 100% for both films and MPR. For detecting meniscal tears, sensitivity was 55% and specificity was 90%, using the filmed images, versus 64% and 85%, respectively, with MPR. These differences were not statistically significant by the sign test. Total time (technologist processing time plus radiologist reading time) for MPR was greater than for film interpretation by a factor of 1.12 (P < .05), and radiologist reading time for MPR was greater by a factor of 1.88 (P < .05). CONCLUSIONS: For sagittal three-dimensional FISP MRI datasets, real-time MPR is comparable with film interpretation for evaluation of ACL and meniscal injuries, but it increases the time required for diagnosis.

Discrimination between sheep antibodies to Brucella melitensis and to Brucella ovis.

When preparations containing smooth Brucella abortus lipopolysaccharide (LPS) were used as antigen in an ELISA, strong positive reactions were obtained with sera from sheep infected with Brucella melitensis or with Brucella ovis. Oxidation of the LPS with sodium metaperiodate greatly reduced the extent of the cross-reactions with antisera to B. ovis, with little effect on the reactions with antisera to smooth B. melitensis. Periodate oxidation of hot saline extract (HSX) antigen of B. ovis markedly reduced its reactivity in ELISA with anti-B. ovis sera and eliminated cross-reactivity with anti-B. melitensis sera. The reactivity of HSX was maintained after treatment with proteinase K. A simple ELISA system, in which replicate samples from a single serum dilution were tested in parallel against both B. ovis HSX antigen and periodate-oxidised smooth phase B. abortus LPS, was evaluated. It was found to discriminate well between antibodies induced by vaccination or virulent infection with B. melitensis strains and those induced by infection with B. ovis.

Internal morphology of human cervical pedicles.

STUDY DESIGN: The internal architecture of cervical spine pedicles was investigated by thin sectioning and digitization of radiographic images. OBJECTIVES: To provide quantitative information on the internal dimensions and cortical shell thicknesses of the middle and lower cervical pedicles. SUMMARY OF BACKGROUND DATA: Although there have been a number of studies presenting data on the external dimensions of the cervical pedicle, little is known regarding its internal architecture and cortical shell thickness along the pedicle axis. METHODS: Twenty-five human cervical vertebrae (C3-C7) were secured to a thin-sectioning machine to produce three 0.7-mm-thick pedicle slices along its axis. Plain radiographs of the pedicle slices were scanned and digitized to facilitate measurement of the internal dimensions. Computer software was specifically developed to determine the external dimensions (i.e., pedicle height and width) and the internal dimensions (i.e., cortical shell thicknesses of the superior, inferior, lateral, and medial walls and the cancellous core height and width) of cervical pedicles. RESULTS: Superior and inferior wall cortical thicknesses of pedicle thin slices were similar, whereas the lateral wall cortical thickness was significantly smaller than the medial wall thickness. The medial cortical shell (average value range: 1.2-2.0 mm) was measured to be 1.4 to 3.6 times as thick as the lateral cortical shell (average value range: 0.4-1.1 mm). When medial and lateral cortical thicknesses were normalized for external dimensions, the combined cortical shell thickness was thinnest at C7 (average value range: 18. 6-25.6% of the external width), and this result was statistically significant when compared with other vertebral levels. CONCLUSIONS: The cervical pedicle is a complex, three-dimensional structure exhibiting extensive variability in internal morphology. Characteristics of the cervical pedicle at different spinal levels must be noted before transpedicular screw fixation.

The cortical shell architecture of human cervical vertebral bodies.

STUDY DESIGN: An anatomic study of cervical vertebral bodies. OBJECTIVES: To provide quantitative information on the cortical shell architecture of the middle and lower cervical vertebral bodies. SUMMARY OF BACKGROUND DATA: Some external dimensions have been measured, but little quantitative data exists for the cortical shell architecture of the vertebral bodies of the cervical spine. METHODS: Twenty-one human cervical vertebral bodies (C3-C7) were sectioned along parasagittal planes into five 1.7-mm thin slices for each vertebra. Radiographs of each slice were digitized, and external and internal dimensions were measured. Averages and standard deviations were computed. Single factor analysis of variance was used to determine significant (P < 0.05) differences between the vertebral levels. RESULTS: The superior endplate was thickest in the posterior region (range 0.74-0.89 mm) and thinnest in the anterior region (range 0.44-0.56 mm). The inferior endplate was thickest in the anterior region (range 0.61-0.81 mm) and thinnest in the posterior region (range 0.49-0.62 mm). In the central region, the superior endplate (range 0.42-0.58 mm) was thinner than the inferior endplate (range 0.53-0.64 mm). Variation with vertebral level was dependent on the dimension studied. CONCLUSIONS: Comprehensive quantitative anatomic data of the middle and lower cervical vertebral bodies have been obtained. This may be useful in improving the understanding of the three-column and other vertebral-fracture theories, the fidelity of the finite element models of cervical spine, and the designs of surgical instrumentation.

Absolute instabilities in a high-order-mode gyrotron traveling-wave amplifier.

The absolute instability is a subject of considerable physics interest as well as a major source of self-oscillations in the gyrotron traveling-wave amplifier (gyro-TWT). We present a theoretical study of the absolute instabilities in a TE01 mode, fundamental cyclotron harmonic gyro-TWT with distributed wall losses. In this high-order-mode circuit, absolute instabilities arise in a variety of ways, including overdrive of the operating mode, fundamental cyclotron harmonic interactions with lower-order modes, and second cyclotron harmonic interaction with a higher-order mode. The distributed losses, on the other hand, provide an effective means for their stabilization. The combined configuration thus allows a rich display of absolute instability behavior together with the demonstration of its control. We begin with a study of the field profiles of absolute instabilities, which exhibit a range of characteristics depending in large measure upon the sign and magnitude of the synchronous value of the propagation constant. These profiles in turn explain the sensitivity of oscillation thresholds to the beam and circuit parameters. A general recipe for oscillation stabilization has resulted from these studies and its significance to the current TE01 -mode, 94-GHz gyro-TWT experiment at UC Davis is discussed.

Mechanical performance of surgical needle holders.

A new quantitative measurement of surgical needle holder performance has been described that records the forces (clamping moment) applied by the needle holder jaws to curved surgical needles. This test has been used to determine the applied clamping forces of four different surgical needle holders made by one manufacturer. By relating the magnitude of the clamping moment of needle holder to the resistance to bending of curved surgical needles, we propose a new scientific basis for selecting surgical needle and needle holders for wound closure.

Biomechanics of a new atraumatic surgical needle holder.

It is the purpose of this report to design, develop, and evaluate a needle holder whose jaws improve needle-holding security without altering the geometry of the curved surgical needle. The configuration of the jaws of this new needle holder is curved, conforming to the curvature of the surgical needle. A biomechanical study of this curved surgical needle holder demonstrates that it holds the curved needle securely without needle deformation.

[Detection of Plasmodium falciparum using the plasmid Pf rep 20 probe (preliminary report)].

A cloned repetitive DNA sequence (rep 20) labeled with 32P was evaluated as diagnostic probe for P. falciparum in 39 blood samples from Hainan and Yunan provinces. Its specificity and sensitivity were studied and compared with total genomic DNA probe isolated from P. f. Hainan Fcc1/HN isolate. The pPF rep 20 probe recognized the DNA of P. f. Hainan, Yunnan and Anhui isolates, but did not hybridize with the DNA of P. vivax, P. cynomolgi, P. knowlesi and P. yoelii. The genomic probe hybridized with the DNA of 3 isolates and cross-hybridized with the DNA of all the other Plasmodium species tested, but did not hybridize with host DNA. The plasmid rep 20 probe was able to detect parasitemia level of 0.001% in 20 microliters blood from culture and 10pg DNA of 3 P. f. isolates after 3 days film exposure. It could hybridize with the blood samples of P. f. patients from Hainan and Yunnan with a sensitivity of 95% (37/39). The genomic probe could detect the same parasitemia and DNA levels as plasmid rep 20 probe for Yunnan and Anhui isolates, and 0.0001% parasitemia and 1 pg DNA for Hainan isolate. It had a sensitivity of 97% (38/39) when used to detect patient samples. The results indicated that plasmid rep 20 probe was specific and rather sensitive to DNA of P. falciparum isolates from China and may be useful in epidemiological studies.

X-ray microfabrication and measurement of a terahertz mode converter.

Mode converters are critical for frequency-tunable terahertz gyrotrons. This study reports the development of a broadband TE(02) mode converter centered at 0.2 THz. An octafeed sidewall coupling structure was employed and the mode purity was analyzed. The converter was built using the technique of x-ray microfabrication. The x rays irradiated on the SU-8 resist and generated a template of very high thickness of 1.295 mm. Pulse electroplating technique was used to deposit copper on the structure along the template. The parts then went through precise machining and the residual resist was removed via high-flux radical etching. A computer-aided diagnostic system was introduced to measure the performance of the converter. Results suggest that the frequency response of resistivity should be taken into consideration for the devices in terahertz region.